Nanocomposite Multifunctional Hydrogel for Suppressing Osteosarcoma Recurrence and Enhancing Bone Regeneration

Abstract

Osteosarcoma (OS) is the most prevalent primary malignancy of bone. Inhibition of OS recurrence and subsequent bone formation after surgery remains a challenge for decades. Innovative biomaterials with dual function of tumor therapy and bone regeneration have emerged as a promising strategy for OS treatment. We developed a bioactive nanoparticle (MDA-NPs) composed of magnesium oxide nanoparticle (M-NPs) core and 2-Aminoethyl methacrylate (2-AM) grafted polydopamine (PDAM) shell. The MDA-NPs were then incorporated into phosphonate modified methacrylamide chitosan (CMP) and polyacrylamide (PAM) to form a double network (DN) hydrogel (NP/CMP@PAM), endowing the hydrogel with excellent photothermal therapy (PTT) ability and sustainable Mg 2+ release kinetics. The hydrogel with 5 mg/mL MDA-NPs (5NP/CMP@PAM) showed balanced photothermal effect, mechanical property, and osteogenesis. 143B could be efficiently inhibited by 5NP/CMP@PAM hydrogel with near-infrared (NIR) laser irradiation, achieving complete suppression of tumor recurrence in vitro and in vivo. The released Mg 2+ efficiently promotes the osteogenic activities of MC3T3-E1 and 5NP/CMP@PAM hydrogels exhibite highly effective bone repair performance in a critical cranial defect rat model. In conclusion, the 5NP/CMP@PAM hydrogel demonstrated   excellent dual functions of suppressing OS recurrence and repairing bone defect. This novel multifunctional bioactive hydrogel provides an encouraging idea of synergistic postoperative treatment of OS.

Keywords: osteosarcoma, photothermal treatment, double network (DN) hydrogel, osteogenic activity, Antitumor